Normal monocytes, keratinocytes and lymphocytes as well as cell lines when activated by antigenic or polyclonal stimulants produce a multiplicity of immunoregulatory mediators with potent biological effects on a wide variety of target cells at concentrations of 10-10 to 10 -15M. Activated macrophages produce interleukin 1 (IL 1) which enhances the proliferation of peanut nonagglutinating (PNA) thymocytes and induces them to produce the lymphokine IL 2, which in turn induces proliferation by PNA+ thymocytes. The IL 1 has pleotrophic effects in that it stimulates hepatocytes to produce serum amyloid A (SAA), is a growth factor for fibroblasts and has endogenous pyrogen activity. Keratinocytes produce a mediator(s) that has the same biological and biochemical properties as IL 1. In addition, this epidermal cell derived thymocyte activating factor (ETAF) as well as IL 1 are chemotactic for neutrophils and monocytes. ETAF and IL 1 also activate neutrophils. IL 1 and or ETAF activities have been detected in the gingival exudate of normal subjects, and even more is detected in exudate obtained from sites of gingival inflammation. IL 1 and ETAF are important in initiating a cascade of interactions between cells and factors that modulate inflammatory responses.